This project covers analytic and methodologic studies aimed at assessing the epidemiology of prostate cancer and clarifying through biochemical and methodologic studies the biological underpinnings of how lifestyle factors influence the risk of prostate cancer. Our efforts relate to a variety of environmental, genetic, and hormonal predictors of risk in special populations. We have conducted a multidisciplinary study in China to assess risk factors for prostate cancer in a low-risk population in order to understand more clearly the reasons for the large racial differences in prostate cancer risk. The study involves collection of multiple biologic samples, with a primary aim of assessing risk factors and how westernization influences the risk of prostate cancer. The study also involves collection of tissue samples to permit precise tumor classification as well as assays of tumor biomarkers, in some cases using newly developed tissue microarray techniques. In addition to specific dietary factors, dietary patterns will be identified to evaluate whether a western-pattern diet in China is related to excess prostate cancer risk. The study is also assessing biological correlates of westernization to look for potential biological links between westernization and excess prostate cancer risk. Data on genotypes and circulating levels of hormones provide a unique opportunity to investigate the interrelationships between serum hormones and genetic variants to gain insights into the functional significance of these genetic markers. In another study of prostate cancer in 15 cities in China, we are assessing the role of soy in prostate cancer by developing a dietary isoflavone index. A population-based survey is currently underway in Ghana, Africa, to assess the burden of prostate cancer in African men. This study will collect clinical/pathological data from over 1,000 men diagnosed with prostate cancer during the last 5 years and screen 1,000 healthy men for prostate cancer by digital rectal examination and prostate specific antigen to evaluate the burden of prostate cancer in west African men. Biological samples collected from these 1,000 healthy men will provide a unique resource to establish the nutritional, hormonal, and genetic profiles of African men. In addition, linking interview data from these 1, 000 healthy subjects with biomarkers from them will produce insights into whether westernization in African men is associated with an adverse metabolic profile (obesity, abdominal obesity, higher levels of insulin, low-density lipoprotein, and insulin-like growth factor I), which have been associated with excess prostate cancer risk. We also are developing plans to assess the relationships of obesity, dietary patterns, insulin resistance, and chronic inflammation with subsequent risk of prostate cancer within the etiologic component of the large Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. This resource is unique in having collected pre-morbid blood and multiple biologic samples over time, permitting an assessment of how hormone and other biomarker levels change as patients approach diagnosis. A methodologic study is currently underway to evaluate whether circulating levels of androgens reflect intraprostatic androgenicity, a key issue in hormonal carcinogenesis of the prostate. This methodologic study will collect samples of fasting blood and snap-frozen fresh tissue (over 4000 pieces) from 650 study subjects in three racial/ethnic groups. Data from this study provide a unique opportunity to investigate the interrelationships between serum and tissue hormones and variants in genes involved in the androgen metabolism pathways to provide critical data for the functional significance of these genetic markers. The collection of tissue samples also provides a unique opportunity for gene expression studies. Benign prostatic hyperplasia and prostate cancer are both common conditions in the prostate cancer but their relationship is unclear. In collaboration with Swedish investigators, through population-based record linkage data on nearly 80,000 men with benign prostatic hyperplasia (BPH), we are assessing the risk of prostate cancer following BPH. In another population-based record linkage study in Sweden, we are determining the relationship between occupation and prostate cancer risk in nearly 37,000 men with prostate cancer.